This project was initiated to use the rat pineal gland as a model system in which to study the regulation of circadian rhythms and the role of cyclic nucleotides in neurotransmission. Cyclic GMP is released from the sympathetic nerve endings in the rat pineal gland in association with exocytosis. Lithium inhibits the response of both cyclic AMP and cyclic GMP to stimulation. Elevated nocturnal levels of N-acetyltransferase require continued activity of the suprachiasmatic nucleus of the hypothalamus. Central depressants can cause a rapid fall in enzyme activity. Light and carbachol both can reduce enzyme activity and reset the circadian mechanism resulting in a phase shift of the pineal rhythm.